Probenecid with methotrexate

METHOTREXATE ANTIGOUT DRUGS -PROBENECID t methotrexate levels Probenecid 1 elimination of methotrexate renally by interfering with tubular secretion in the proximal tubule and also 1 protein binding of methotrexate (a relatively minor effect). Probenecid competes with methotrexate for renal elimination Avoid co-administration if possible if not possible, 1 dose of methotrexate and monitor FBC closely... 

Probenecid competes with methotrexate for renal tubular secretion, and can cause severe hematological toxicity. 

Methotrexate, a weak acid, depends upon active tubular excretion in the proximal tubule for efficient elimination. Probenecid competes with methotrexate for binding to the proximal tubule transporter and thereby decreases the rate of clearance of methotrexate. The answer is... 

Interference with active transport. Organic acids are passed from the blood into the urine by active transport across the renal tubular epithelium. Penicillin is mostly excreted in this way. Probenecid, an organic acid that competes successfully with penicillin for this transport system, may be used to prolong the action of penicillin when repeated administration is impracticable, e.g. in sexually transmitted diseases, where compliance is notoriously poor. Interference with renal excretion of methotrexate by aspirin, of zidovudine by probenecid and of digoxin by quinidine, contribute to the potentially harmful interactions with these combinations. 

Concomitant use of heparin and oral anticoagulants can increase the risk for bleeding due to the antiplatelet effect of aspirin. In addition, use with alcohol can increase the risk of Gl bleeding. / spirin displaces a number of drugs (e.g., tolbutamide, nonsteroidal anti-inflammatory drugs [NSAIDs], methotrexate, phenytoin, and probenecid) from protein binding sites in the blood. Corticosteroid use can reduce serum salicylate levels by increasing the clearance of aspirin. 

Clinically important, potentially hazardous interactions with aspirin, methotrexate, probenecid... 

No. Methotrexate increases serum uric acid, and concurrent therapy with probenecid results in increased uricosuria. The levels of methotrexate may also be increased, through competition with probenecid for the organic acid secretory system. The probability of methotrexate-induced uric acid neuropathy is increased by the administration of probenecid. 

Severe somnolence and lethargy may occur with combinations of zidovudine and acyclovir. Concomitant cyclosporine enhances nephrotoxicity. Probenecid decreases acyclovir renal clearance and prolongs the plasma t of elimination. Acyclovir may decrease the rerml clearance of other drugs eliminated by active renal secretion (e.g., methotrexate. ... 

Increased risk of bleeding with anticoagulants. Increased risk of Gl ulceration with alcohol, corticosteroids, phenylbutazone, oxyphenbutazone. Decreases uricosurea effects of probenecid and sulfinpyrazone and diuretic effects of spironolactone. Decreases absorption of tetracycline. Increases plasma levels of methotrexate. 

Cephalosporins Dapsone Methotrexate Penicillins Quinolones Probenecid Serum levels of drug affected raised possibility of toxicity with some drugs... 

A three to fourfold increase in serum methotrexate levels at 24 hours was also seen in 4 patients given probenecid. Pretreatment with probenecid (500 mg every 6 hours for 5 doses) doubled the serum methotrexate levels of another 4 patients. Severe and life-threatening pancytopenia occurred when a woman taking low-dose methotrexate 7.5 mg weekly for rheumatoid arthritis was given probenecid. She also had renal impairment, hy-poalbuminaemia and was taking salsalate (a salicylic acid derivative). ... 

An established and clinically important interaction. A marked increase in both the therapeutic and toxic effects of methotrexate can occur, apparently even with low doses if other risk factors are present. Anticipate the need to reduce the dosage of the methotrexate and monitor the effects well if probenecid is used concurrently, or avoid the combination. 

Drug interactions occur with many commonly prescribed medications and are mostly due to naproxen s effects on renal prostaglandins and the associated changes in kidney filtration rate, although many other mechanisms exist. Many drug interactions exist, with examples being ACE inhibitors, beta blockers, methotrexate, lithium, probenecid, antiplatelet agents, diuretics, and vancomycin. 

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